Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate

Badawi, Alaa; Liu, Yingying; Eldeen, Mazen B.; Morrow, Willard; Razak, Zaineb R.; Maradeo, Marie E.; Badr, Mostafa Z.

doi:10.1093/carcin/bgi186

Cited by 12 publications

(5 citation statements)

References 47 publications

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“…Interestingly, 335‐hMSCs have lower basal levels of PTGS2 (COX‐2), and fail to upregulate this gene in response to several stimuli. Of note, PTGS2 has been proposed to contribute to the establishment of the senescence phenotype and is known to be upregulated during both replicative and stress‐induced senescence of cultured fibroblasts , and also during organismal aging . However, it remains unclear whether the catalytic activity of PTGS2 is involved in the aging process , and paradoxically, constitutive overexpression of PTGS2 has been linked with cellular resistance to senescence in cancer cells .…”

Section: Discussionmentioning

confidence: 99%

miR-335 Correlates with Senescence/Aging in Human Mesenchymal Stem Cells and Inhibits Their Therapeutic Actions Through Inhibition of AP-1 Activity

et al. 2014

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MicroRNAs (miRNAs), small non-coding RNAs, regulate gene expression primarily at the posttranscriptional level. We previously found that miR-335 is critically involved in the regulation and differentiation capacity of human mesenchymal stem cells (hMSCs) in vitro. In this study, we investigated the significance of miR-335 for the therapeutic potential of hMSCs. Analysis of hMSCs in ex vivo culture demonstrated a significant and progressive increase in miR-335 that is prevented by telomerase. Expression levels of miR-335 were also positively correlated with donor age of hMSCs, and were increased by stimuli that induce cell senescence, such as γ-irradiation and standard O2 concentration. Forced expression of miR-335 resulted in early senescence-like alterations in hMSCs, including: increased SA-β-gal activity and cell size, reduced cell proliferation capacity, augmented levels of p16 protein, and the development of a senescent-associated secretory phenotype (SASP). Furthermore, overexpression of miR-335 abolished the in vivo chondro-osseous potential of hMSCs, and disabled their immunomodulatory capacity in a murine experimental model of lethal endotoxemia. These effects were accompanied by a severely reduced capacity for cell migration in response to pro-inflammatory signals and a marked reduction in Protein Kinase D1 (PRKD1) phosphorylation, resulting in a pronounced decrease of AP-1 activity. Our results demonstrate that miR-335 plays a key role in the regulation of reparative activities of hMSCs and suggests that it might be considered a marker for the therapeutic potency of these cells in clinical applications.

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Section: Discussionmentioning

confidence: 99%

miR-335 Correlates with Senescence/Aging in Human Mesenchymal Stem Cells and Inhibits Their Therapeutic Actions Through Inhibition of AP-1 Activity

et al. 2014

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“…Pharmacological inhibition of the cysteinyl leukotrienes via LT antagonists, LY255283 and montelukast sodium, or ALOX5 inhibitor, BW-B70C, reduced the profibrotic effect of senescent cells on naive fibroblasts in vitro ( Wiley et al, 2019 ) and attenuated TNFα-induced up-regulation of SA-β-Gal, p53, p21, and PAI-1 expression in primary human chondrocytes associated with osteoarthritis ( Song et al, 2018 ). Increase in COX-2 activity has been shown to be associated with aging ( Badawi et al, 2005 ; Chung et al, 1999 ; Baek et al, 2001 ). For example, COX-2 expression was upregulated in kidney, liver, heart and prostrate in old rodents ( Hayek et al, 1997 ; Kim et al, 2001 ; Badawi et al, 2004 ; Choi et al, 2014 ; Tung et al, 2015 ), and in aging human tissues as well, especially kidney and skin ( Melk et al, 2004 ; Kang et al, 2006 ; Surowiak et al, 2014 ).…”

Section: Major Lipid Players In Senescencementioning

confidence: 99%

Lipids as Regulators of Cellular Senescence

Hamsanathan

Gurkar

2022

Front. Physiol.

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Lipids are key macromolecules that perform a multitude of biological functions ranging from maintaining structural integrity of membranes, energy storage, to signaling molecules. Unsurprisingly, variations in lipid composition and its levels can influence the functional and physiological state of the cell and its milieu. Cellular senescence is a permanent state of cell cycle arrest and is a hallmark of the aging process, as well as several age-related pathologies. Senescent cells are often characterized by alterations in morphology, metabolism, chromatin remodeling and exhibit a complex pro-inflammatory secretome (SASP). Recent studies have shown that the regulation of specific lipid species play a critical role in senescence. Indeed, some lipid species even contribute to the low-grade inflammation associated with SASP. Many protein regulators of senescence have been well characterized and are associated with lipid metabolism. However, the link between critical regulators of cellular senescence and senescence-associated lipid changes is yet to be elucidated. Here we systematically review the current knowledge on lipid metabolism and dynamics of cellular lipid content during senescence. We focus on the roles of major players of senescence in regulating lipid metabolism. Finally, we explore the future prospects of lipid research in senescence and its potential to be targeted as senotherapeutics.

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“…One of the major reasons are the impaired DNA repair mechanisms which have been described in several studies and have been associated with the initiation of ageassociated diseases and progeroid syndromes (Hasty et al, 2003;Lieber and Karanjawala, 2004). Furthermore, dysregulated immune and inflammatory responses have been already documented both in humans and mouse with increasing age (Badawi et al, 2004;Kovaiou et al, 2007).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

The skin as a mirror of the aging process in the human organism – State of the art and results of the aging research in the German National Genome Research Network 2 (NGFN-2)

Makrantonaki

Zouboulis

2007

Experimental Gerontology

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As our society is growing older, the consequences of aging have begun to gain particular attention. Improvement of quality of life at old age and prevention of age-associated diseases have become the main focus of the aging research. The process of aging in humans is complex and underlies multiple influences, with the probable involvement of heritable and various environmental factors. In particular, hormones are decisively involved in the generation of aging. Over time, important circulating hormones decline due to a reduced secretion of the pituitary, the adrenal glands and the gonads or due to an intercurrent disease. Among them, serum levels of growth factors and sexual steroids show significant aging-associated changes. Within the scope of the Explorative Project 'Genetic aetiology of human longevity' supported by the German National Genome Research Network 2 (NGFN-2) an in vitro model of human hormonal aging has been developed. Human SZ95 sebocytes were maintained under a hormone-substituted environment consisting of growth factors and sexual steroids in concentrations corresponding to those circulating in 20- and in 60-year-old women. Eight hundred and ninety-nine genes showed a differential expression in SZ95 sebocytes maintained under the 20- and 60-year-old hormone mixture, respectively. Among them genes were regulated which are involved in biological processes which are all hallmarks of aging. The most significantly altered signaling pathway identified was that of the transforming growth factor-beta (TGF-beta). A disturbed function of this cascade has been associated with tumorigenesis, i.e. in pancreatic, prostate, intestine, breast, and uterine cancer. Interestingly, genes expressed in signaling pathways operative in age-associated diseases such as Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and amyotrophic lateral sclerosis (ALS) were also identified. These data demonstrate that skin and its appendages may represent an adequate model for aging research. Hormones interact in a complex fashion, and aging may be partly attributed to the changes in their circulating blood levels. Furthermore, a disturbed hormone status may partially act towards the manifestation of neurodegenerative diseases. Thus, these results could be a basis for an integrated and interdisciplinary approach to the analysis of the aging process.

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Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate

Cited by 12 publications

References 47 publications

miR-335 Correlates with Senescence/Aging in Human Mesenchymal Stem Cells and Inhibits Their Therapeutic Actions Through Inhibition of AP-1 Activity

miR-335 Correlates with Senescence/Aging in Human Mesenchymal Stem Cells and Inhibits Their Therapeutic Actions Through Inhibition of AP-1 Activity

Lipids as Regulators of Cellular Senescence

The skin as a mirror of the aging process in the human organism – State of the art and results of the aging research in the German National Genome Research Network 2 (NGFN-2)

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